The latest and largest systematic review on intravenous iron administration finds that it is associated with an increased risk of infections.

In the meta-analysis of 154 randomized trials published from 1966 to 2021 including 32,920 patients, intravenous iron was significantly associated with a 17% increased risk of infection compared with oral iron or no iron, Akshay A. Shah, MSc, of John Radcliffe Hospital in Oxford, UK, and colleagues reported in JAMA Network Open. In absolute terms, 17 more individuals per 1000 population will experience an infection when intravenous iron is administered. Patients with inflammatory bowel disease, who commonly receive immunosuppressive and biological drugs, had a significant 73% increased risk of infection. Results were similar across iron preparations and single vs multiple dose regimens.

Intravenous iron also was significantly associated with a mean 0.57 g/dL increase in hemoglobin levels and a 7% decreased risk of red blood cell transfusion. There was no evidence of an effect on mortality or hospital length of stay, but the confidence intervals were wide, the investigators reported.

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Using the GRADE approach, the investigators judged the quality of evidence to be moderate. Infection was variably defined, however, precluding some meaningful analyses, they noted.

A biological link is plausible. Intravenous iron increases the levels of circulating non-transferrin-bound iron, which may impair T-cell and neutrophil function, promote pathogen growth, and predispose patients to infection, Shah and colleagues explained.

“Clinical guidelines increasingly advocate the use of intravenous iron, and clinicians and policy makers should recognize that the benefits of treating anemia may need to be balanced against the risk of developing infection,” Shah’s team stated.

In an accompanying editorial, Deborah Rund, MD, of Hebrew University-Hadassah Medical Organization in Jerusalem, Israel, expressed caution.

“In summary, the issue of infection risk from IV iron is not simple to unravel,” she wrote. “For the present, clinicians should be cautious and defer IV iron therapy during acute infections, as has been suggested. More conclusive evidence is required to guide us on the use of this important therapeutic modality.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Shah AA, Donovan K, Seeley C, et al. Risk of infection associated with administration of intravenous iron: a systematic review and meta-analysis. JAMA Netw Open. Published online November 12, 2021. doi:10.1001/jamanetworkopen.2021.33935

Rund D. Intravenous iron and infection risk—still an unanswered question. JAMA Netw Open. Published online November 12, 2021. doi:10.1001/jamanetworkopen.2021.34453